The goal of the Chemistry Core is to provide a complete support of the PPG activities in terms of access to synthetic molecular probes to be used for the investigation of general anesthetic binding sites of ligand-gated receptors of y-aminobutyric acid (GABAA) acetylcholine and serotonin . The probes will represent analogs of four major classes of anesthetics that interact with these receptors, and will be used for studying the corresponding multiple binding sites on these receptors. The most important aspects of our structural and synthetic design is to produce photoactivatable analogs with minimal structure alteration to retain high binding affinity and to ensure the analogous modes of binding to those of the parent molecules, and to permit synthesis of the radiolabeled molecules with the highest specific radioactivity possible. We will synthesize analogs of the following groups of receptor ligands: (i) propofol, a GABAA receptor ligand and a potent clinically used general anesthetic;(ii) barbituric acid, a ligand of GABAA and nicotinic acetylcholine receptors; (iii) long-chain aliphatic and aromatic alcohols, ligands that have binding sites on all members of the superfamily;and (iv) etomidate, another potent ligand that binds in the anesthetic site of GABAA receptors. In addition, when needed, we will resynthesize any needed ligand that has previously been used by the PPG. The leadership of the Core has been assumed by Dr. Bruzik in Chicago. A small part of the Core remains at MGH for the distribution and maintenance of stocks of existing photolabels. Administratively, the Core is structured with the Program Director as PI and a subcontract to the University of Illinois, Chicago. RELEVANCE (See Instmctions):